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This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 107/4/1059    most recent 90785.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Graham, D. A. Articles by Rush, J. W. E. PubMed PubMed Citation Articles by Graham, D. A. Articles by Rush, J. W. E.

Cyclooxygenase and thromboxane/prostaglandin receptor contribute to aortic endothelium-dependent dysfunction in aging female spontaneously hypertensive rats

Department of Kinesiology, Faculty of Applied Health Sciences, University of Waterloo, Waterloo, Ontario, Canada

Submitted 18 June 2008 ; accepted in final form 17 August 2009

Cyclooxygenase (COX)-derived vasoconstrictory prostanoids contribute to impaired endothelium-dependent vasorelaxation in aging male (m) spontaneously hypertensive rats (SHR); however, vasomotor responses in aging female (f) SHR and sex differences in aging SHR are unknown. Examining mechanisms governing dysfunction in aging fSHR will contribute to understanding sex-dependent vascular complications in advanced hypertension. Aortic endothelium-dependent relaxation dose responses (ACh) of 16- and 30-wk-old mSHR and fSHR and normotensive Wistar-Kyoto rats were examined in the absence (no drug control) and presence of COX inhibition [indomethacin (Indo)] and thromboxane/prostaglandin receptor inhibition (SQ-29548). No drug control-treated 16-wk mSHR exhibited considerable blunting of the peak relaxation response to ACh (e.g., 77 ± 4% relaxation to 10^–5 mol/l) vs. Wistar-Kyoto controls (89 ± 6%), and greater dysfunction occurred in 30-wk mSHR (63 ± 2%). Interestingly, ACh relaxations of fSHR were unimpaired at 16 wk (101 ± 2% to 10^–5 mol/l), but blunted in 30 wk (76 ± 4%). Indo and SQ-29548 restored robust ACh vasorelaxation in all groups (e.g., 113 ± 3 and 112 ± 3%, respectively, in Indo- and SQ-29548-treated 30-wk fSHR). Aortic COX-1 protein expression was elevated by 75% in 30-wk vs. 16-wk fSHR, whereas group-averaged ACh-stimulated aortic PGI₂ release (assessed as 6- keto-PGF₁) was 30% greater in 30-wk vs. 16-wk fSHR (9,926 ± 890 vs. 7,621 ± 690 pg·ml^–1·mg dry wt^–1), although this did not reach significance (P = 0.0758). Dramatic deterioration of endothelium-dependent vasomotor function in fSHR across this age range involves COX and thromboxane/prostaglandin receptor, supporting a mechanism of impairment similar to that which occurs in aging mSHR.

endothelium-derived contracting factor; prostanoid; nitric oxide; sex difference; endothelium-dependent relaxation; prostaglandin I₂; thromboxane/prostaglandin receptor; SQ-29548